Intravitreal triple therapy with vancomycin, ceftazidime, and moxifloxacin for bacterial endophthalmitis: A Twelve-year experience.

PURPOSE: Increasing rates of antibiotic resistance in endophthalmitis have been reported. This study examines outcomes of triple therapy with intravitreal vancomycin, ceftazidime, and moxifloxacin for endophthalmitis. METHODS: Retrospective, consecutive series of all patients treated with abovementioned intravitreal antibiotics from January 2009 to June 2021. Percentages of eyes attaining greater than or equal to 20/200 and 20/50 Snellen visual acuities and adverse events were evaluated. RESULTS: 112 eyes met inclusion criteria. 63 of 112 eyes (56%) achieved a visual acuity of 20/200 during follow-up, with 39 (35%) returning to at least 20/50. In subgroup analysis, 23 of 24 (96%) eyes with post-cataract endophthalmitis obtained ≥ 20/200 acuity and 21 of 24 (88%) obtained ≥ 20/50 acuity during follow-up. There were no cases of macular infarction. CONCLUSIONS: Intravitreal moxifloxacin (160 µg/0.1 mL) was well tolerated as an adjunct to vancomycin and ceftazidime for bacterial endophthalmitis. Use of this novel combination offers several theoretical advantages compared to standard therapy with two antibiotics, including expanded gram-negative coverage and potential synergy, and may be particularly valuable in geographies where the local antibiogram supports empiric use. Further study is merited to verify the safety and efficacy profile.

The Mydriatic Red Eye as the Initial Presentation of Syphilis.

BACKGROUND: Syphilis is a sexually transmitted infection that has been increasing in prevalence since the early 2000s. Ocular involvement occurs in a minority of patients and must be in the differential diagnosis for patients who present with red eye and uveitis. CASE REPORT: A 29-year-old woman presented to the emergency department with a painful, mydriatic red eye. Review of systems revealed a rash as well as a recent genital lesion and, on further questioning, she admitted to a history of intravenous drug use and high-risk sexual activity. Ophthalmology was consulted and the patient was diagnosed with bilateral uveitis. Serologic testing was positive for syphilis, and she was admitted and treated with intravenous penicillin, with resolution of her uveitis. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Red eye is a common ocular symptom in patients presenting to the emergency department. The differential diagnosis of the red eye is broad and can range from benign etiologies, such as conjunctivitis, to life- and sight-threatening conditions, such as endogenous endophthalmitis. Systemic diseases such as syphilis may present with primarily ocular symptoms, and ocular syphilis must be identified and managed appropriately to prevent devastating sequelae.

Superior ophthalmic vein thrombosis: A rare complication of Graves' orbitopathy.

Superior ophthalmic vein thrombosis is a rare, life- and sight-threatening complication of both infectious and inflammatory orbital disease as well as hypercoagulable state. Only one case of superior ophthalmic vein thrombosis due to thyroid eye disease has been reported in the literature. This article describes the diagnosis and management of a case of superior ophthalmic vein thrombosis due to Graves' orbitopathy. Early diagnosis is critical to facilitate timely therapeutic intervention. Superior ophthalmic vein thrombosis should be considered in the differential diagnosis of acute on chronic proptosis in the setting of Graves' orbitopathy, and may represent and under-recognized and under-diagnosed clinical entity.

Hybrid Neurofibroma/Schwannoma of the Supraorbital Nerve: Clinicopathologic Correlation of a Rare Tumor.

Benign peripheral nerve sheath tumors such as schwannoma and neurofibroma have long been considered distinct entities. Recently, hybrid tumors demonstrating combined morphological features of neurofibroma and schwannoma have been described, primarily in dermal locations. Only 1 case of hybrid peripheral nerve sheath tumor of the orbit has been reported in the literature. Hybrid morphology is important to recognize because of its association with the neurofibromatoses, including schwannomatosis; however, the paucity of literature on orbital hybrid peripheral nerve sheath tumor poses a diagnostic challenge. This article describes a case of hybrid neruofibroma/schwannoma of the orbit arising from the supraorbital nerve with clinicopathologic correlation.

SOX4 interacts with EZH2 and HDAC3 to suppress microRNA-31 in invasive esophageal cancer cells.

BACKGROUND: Tumor metastasis is responsible for 90% of cancer-related deaths. Recently, a strong link between microRNA dysregulation and human cancers has been established. However, the molecular mechanisms through which microRNAs regulate metastasis and cancer progression remain unclear. METHODS: We analyzed the reciprocal expression regulation of miR-31 and SOX4 in esophageal squamous and adenocarcinoma cell lines by qRT-PCR and Western blotting using overexpression and shRNA knock-down approaches. Furthermore, methylation studies were used to assess epigenetic regulation of expression. Functionally, we determined the cellular consequences using migration and invasion assays, as well as proliferation assays. Immunoprecipitation and ChIP were used to identify complex formation of SOX4 and co-repressor components. RESULTS: Here, we report that SOX4 promotes esophageal tumor cell proliferation and invasion by silencing miR-31 via activation and stabilization of a co-repressor complex with EZH2 and HDAC3. We demonstrate that miR-31 is significantly decreased in invasive esophageal cancer cells, while upregulation of miR-31 inhibits growth, migration and invasion of esophageal adenocarcinoma (EAC) and squamous cell carcinoma (ESCC) cell lines. miR-31, in turn, targets SOX4 for degradation by directly binding to its 3'-UTR. Additionally, miR-31 regulates EZH2 and HDAC3 indirectly. SOX4, EZH2 and HDAC3 levels inversely correlate with miR-31 expression in ESCC cell lines. Ectopic expression of miR-31 in ESCC and EAC cell lines leads to down regulation of SOX4, EZH2 and HDAC3. Conversely, pharmacologic and genetic inhibition of SOX4 and EZH2 restore miR-31 expression. We show that SOX4, EZH2 and HDAC3 form a co-repressor complex that binds to the miR-31 promoter, repressing miR-31 through an epigenetic mark by H3K27me3 and by histone acetylation. Clinically, when compared to normal adjacent tissues, esophageal tumor samples show upregulation of SOX4, EZH2, and HDAC3, and EZH2 expression is significantly increased in metastatic ESCC tissues. CONCLUSIONS: Thus, we identified a novel molecular mechanism by which the SOX4, EZH2 and miR-31 circuit promotes tumor progression and potential therapeutic targets for invasive esophageal carcinomas.

BILATERAL CHOROIDAL VASCULAR MALFORMATIONS IN HEREDITARY HEMORRHAGIC TELANGIECTASIA.

PURPOSE: To describe a case of bilateral choroidal vascular malformations in a patient with hereditary hemorrhagic telangiectasia. METHODS: Case report. RESULTS: A 78-year-old man with hereditary hemorrhagic telangiectasia was incidentally noted to have focal, large deep choroidal vessels on optical coherence tomography with corresponding elevation of the overlying retina. Indocyanine green angiography revealed dilated, intensely fluorescent vessels in arterial phase emptying into massively dilated choroidal veins consistent with choroidal arteriovenous malformation. CONCLUSION: This case presents multimodal imaging findings of choroidal arteriovenous malformations in hereditary hemorrhagic telangiectasia. Choroidal vascular malformations may represent an underrecognized clinical feature of this syndrome.

Anti-inflammatory Pharmacotherapy for the Prevention of Cystoid Macular Edema After Cataract Surgery.

PURPOSE: To elucidate strategies for and controversies surrounding the use of anti-inflammatory medications after uneventful cataract surgery, with a focus on the prevention of irreversible vision loss due to cystoid macular edema (CME). DESIGN: Perspective. METHODS: Expert commentary on the management of inflammation after cataract surgery. Discussion includes combination therapy with corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs), dosing strategies, and emerging therapies. RESULTS: While prescribing both NSAIDs and corticosteroids for cataract surgery is common, these classes have overlapping mechanisms. Combination therapy may speed visual recovery, but there remains little evidence for improved long-term visual outcomes from NSAIDs. The last 2 decades have seen increasing data on potential benefits of pretreatment with NSAIDs 1-3 days prior to cataract surgery. Simultaneously, newly approved "dropless" delivery systems hold promise, and clinical trials are ongoing to assess outcomes of such formulations. CONCLUSIONS: Optimal pharmacologic treatment for inflammation after cataract surgery remains controversial. A consensus definition for clinically significant CME may facilitate the comparison of anti-inflammatory drugs. And there remains a need for well-designed trials examining both topical and extended-release drug-delivery systems to refine the treatment paradigm.

Chronic endophthalmitis from Aquamicrobium lusatiense.

PURPOSE: To report a case of chronic endophthalmitis caused by Aquamicrobium lusatiense following phacoemulsification surgery. OBSERVATIONS: A 71 year-old woman was referred for chronic ocular inflammation after cataract surgery. Serologic testing was negative for common infectious etiologies. Her condition deteriorated on immune-modulating therapy prompting vitreous biopsy, which confirmed infection with A. lusatiense. She was managed successfully with intravitreal antibiotic pharmacotherapy and intraocular lens explantation. CONCLUSION AND IMPORTANCE: This is the first reported case of A. lusatiense causing endophthalmitis, or disease in a human, in the literature.

Acute macular neuroretinopathy following Pfizer-BioNTech COVID-19 vaccination.

PURPOSE: To describe a case of acute macular neuroretinopathy (AMN) in a patient immediately following administration of the Pfizer-BioNTech COVID-19 vaccine. OBSERVATIONS: The patient complained of paracentral scotoma supported by paracentral visual field loss on multiple Humphrey visual fields that corresponded to outer retinal pathology on optical coherence tomography. The patient's symptoms resolved without treatment. CONCLUSIONS AND IMPORTANCE: We conclude that the clinical testing demonstrated findings consistent with AMN. AMN may be an exceedingly rare adverse ocular effect of a novel vaccine and likely only in the setting of multiple other risk factors. Despite this, we strongly recommend vaccination against COVID-19.

Iris anomalies and the incidence of ACTA2 mutation.

BACKGROUND: Central cysts of the iris pigment epithelium, or iris flocculi, are frequently reported in the literature in association with thoracic aortic aneurysm and dissection due to smooth muscle alpha-actin 2 (ACTA2) mutations. Children with ACTA2 mutations may also present with congenital mydriasis. We report our experience regarding the frequency of ACTA2 mutation in children with the above iris anomalies. METHODS: This is a retrospective, consecutive case series of all children presenting for iris flocculi or congenital mydriasis at a single tertiary centre from October 2012 to December 2016. RESULTS: 13 children with iris flocculi and 3 with congenital mydriasis presented during the study period. 10 children with iris flocculi completed genetic testing, and none were positive for ACTA2 mutation. All children with congenital mydriasis presented with a multisystem smooth muscle dysfunction syndrome; two of these three children tested positive for missense R179 ACTA2 mutations. CONCLUSIONS: In this series, ACTA2 mutation or copy number variation was not detected in children presenting for iris flocculi, whereas congenital mydriasis was associated with R179 mutation in both cases that tested positive for ACTA2 mutation. The case of congenital mydriasis without typical cardiac features of the R179 ACTA2 phenotype or intracranial vasculopathy was negative for ACTA2 mutation. While all children presenting with these iris anomalies should be offered a genetic evaluation, incidence data should inform genetic counselling, particularly in the absence of a family history of aneurysm or sudden death, or systemic signs of smooth muscle dysfunction.

Clinical and imaging characteristics of posterior column ataxia with retinitis pigmentosa with a specific FLVCR1 mutation.

BACKGROUND: Posterior column ataxia retinitis pigmentosa (PCARP) with feline leukemia virus subgroup C cellular receptor 1 (FLVCR1) gene mutation is a rare disorder with significant ophthalmic features. MATERIALS AND METHODS: We conducted a retrospective case series study of patients diagnosed with PCARP and genetic testing positive for FLVCR1 mutation between 1 January 2015 and 1 October 2017 at the Children's Hospital of Pittsburgh. Clinical charts, visual fields, fundus autofluorescence, and spectral-domain optical coherence tomography (SD-OCT) were reviewed. RESULTS: Seven patients from three families were identified to have PCARP and FLVCR1 mutation. The median age at presentation was 13 years (range, 7-28 years). Common clinical exam findings were astigmatism, cataracts, and vitreous syneresis. Funduscopy on all patients revealed bull's eye maculopathy, retinal vessels attenuation, and bone spicule changes in the peripheral retina. Fundus autofluorescence showed bilateral hyperautofluorescent rings. SD-OCT demonstrated morphological changes, which differed based on age. The youngest sibling family exhibited peripheral loss, but subfoveal preservation of the outer retinal layers. These layers were lost in the oldest sibling family. Visual fields loss paralleled SD-OCT findings. CONCLUSION: There is limited published ophthalmic data on FLVCR1-related PCARP. We describe clinical and retinal imaging features in the one of the largest cohorts of affected patients in the literature. Given the availability of genetic testing for this phenotype, testing for FLVCR1 mutations should be considered in pediatric and adult patients with sensory ataxia and retinitis pigmentosa.

Outcomes Disparities between Black and White Populations in the Surgical Management of Glaucoma.

African descent is a well-documented risk factor for glaucoma development, progression, and medical and surgical failure. We reviewed the literature for evidence of outcomes disparities between Black and White populations after trabeculectomy, Ex-PRESS shunt, viscocanalostomy, canaloplasy, tube shunt, laser trabeculoplasty, and cyclophotocoagulation. There are reports of decreased surgical success in Black patients after trabeculectomy, Ex-PRESS shunt, tube-shunt, and canaloplasty. At this time, there is no strong evidence that any procedure is more effective for intraocular pressure control than standard trabeculectomy for Black patients. Furthermore, there is insufficient evidence to recommend any particular secondary intervention over another, despite differences in inflammation and bleb-dependence. There is a need for randomized, controlled trials to assess race as a risk factor for failure after non-penetrating filtration surgery (NPFS). There is also a need for data on the efficacy of minimally invasive glaucoma surgery (MIGS) in Black populations.

Management of frontal sinusitis-associated subperiosteal abscess in children less than 9 years of age.

PURPOSE: To investigate practice patterns for cases of subperiosteal abscess (SPA) with concomitant frontal sinusitis to identify factors favorable to medical management in children <9 years of age. METHODS: The medical records of all pediatric cases of orbital and periorbital cellulitis admitted at a tertiary care center from 1999-2014 were reviewed retrospectively. Cases were included if radiography demonstrated sinusitis-associated SPA in children <9 years of age. Cases of SPA with ipsilateral frontal sinusitis were compared to cases of SPA without ispilateral frontal sinus involvement. RESULTS: A total of 21 cases with ipsilateral frontal sinusitis and 76 without were included. Patients with frontal sinusitis had a higher incidence of nonmedial SPA compared to those without frontal sinus involvement (6/21 vs 5/76, P = 0.01). Yet a majority of SPAs in the frontal sinusitis group were located medially (15/21 [71%]). All patients with superior or superomedial SPA underwent early surgical intervention. However, 14 of 15 patients (93%) in the frontal sinusitis cohort with medial SPAs were managed successfully with medical therapy alone. CONCLUSIONS: Medical management of frontal sinusitis-associated SPA appears safe for select children <9 years of age with medial abscess. Although frontal sinusitis is cited as a criterion for surgical drainage of SPA, this criterion should be refined to frontal sinusitis with superiorly located abscesses.